Induction of monocyte chemoattractant protein-1 in HIV-1 Tat-stimulated astrocytes and elevation in AIDS dementia
Tóm tắt
Activated monocytes release a number of substances, including inflammatory cytokines and eicosanoids, that are highly toxic to cells of the central nervous system. Because monocytic infiltration of the central nervous system closely correlates with HIV-1-associated dementia, it has been suggested that monocyte-derived toxins mediate nervous system damage. In the present study, we show that the HIV-1 transactivator protein Tat significantly increases astrocytic expression and release of monocyte chemoattractant protein-1 (MCP-1). Astrocytic release of β-chemokines, which are relatively less selective for monocytes, including RANTES, macrophage inflammatory protein-1α, and macrophage inflammatory protein-1β, was not observed. We also show that MCP-1 is expressed in the brains of patients with HIV-1-associated dementia and that, of the β-chemokines tested, only MCP-1 could be detected in the cerebrospinal fluid of patients with this condition. Together, these data provide a potential link between the presence of HIV-1 in the brain and the monocytic infiltration that may substantially contribute to dementia.
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H A Gelbard, L G Epstein Curr Opin Pediatr 7, 655–662 (1995).
A Ueda, K Okuda, S Ohno, A Shirai, T Igarashi, K Matsunaga, J Fukushima, S Kawamoto, Y Ishigatsubo, T Okubo J Immunol 153, 2052–2063 (1994).
E K Azuma, A You, T Matsushima, T Kasahara, H Mizoguchi, M Saito, F Takaku, S Kitagawa Exp Hematol 24, 169–175 (1996).
M E Fuentes, S K Durham, M R Swerdel, A C Lewin, D S Barton, J R Megill, R Bravo, S A Lira J Immunol 155, 5769–5776 (1995).
J R Lokensgard, G Gekker, L C Ehrlich, S Hu, C C Chao, P K Peterson J Immunol 158, 2449–2455 (1997).
H K Parmentier, D F van Wichen, F H Mayling, J Goudsmit, H J Schurman Am J Pathol 141, 1209–1216 (1992).